Targeting CD24 for treatment of colorectal and pancreatic cancer by monoclonal antibodies or small interfering RNA

Eyal Sagiv, Alex Starr, Uri Rozovski, Rami Khosravi, Peter Altevogt, Timothy Wang, Nadir Arbere

Research output: Contribution to journalArticlepeer-review

Abstract

CD24 is a potential oncogene reported to be overexpressed in a large variety of human malignancies. We have shown that CD24 is overexpressed in 90% of colorectal tumors at a fairly early stage in the multistep process of carcinogenesis. Anti-CD24 monoclonal antibodies (mAb) induce a significant growth inhibition in colorectal and pancreatic cancer cell lines that express the protein. This study is designed to investigate further the effects of CD24 down-regulation using mAb or small interfering RNA in vitro and in vivo. Western blot analysis showed that anti-CD24 mAb induced CD24 protein down-regulation through lysosomal degradation. mAb augmented growth inhibition in combination with five classic chemotherapies. Xenograft models in vivo showed that tumor growth was significantly reduced in mAb-treated mice. Similarly, stable growth inhibition of cancer cell lines was achieved by down-regulation of CD24 expression using short hairpin RNA (shRNA). The produced clones proliferated more slowly, reached lower saturation densities, and showed impaired motility. Most importantly, down-regulation of CD24 retarded tumorigenicity of human cancer cell lines in nude mice. Microarray analysis revealed a similar pattern of gene expression alterations when cells were subjected to anti-CD24 mAb or shRNA. Genes in the Ras pathway, mitogen-activated protein kinase, or BCL-2 family and others of oncogenic association were frequently down-regulated. As a putative new oncogene that is overexpressed in gastrointestinal malignancies early in the carcinogenesis process, CD24 is a potential target for early intervention in the prevention and treatment of cancer.

Original languageEnglish
Pages (from-to)2803-2812
Number of pages10
JournalCancer Research
Volume68
Issue number8
DOIs
StatePublished - 15 Apr 2008

Fingerprint

Dive into the research topics of 'Targeting CD24 for treatment of colorectal and pancreatic cancer by monoclonal antibodies or small interfering RNA'. Together they form a unique fingerprint.

Cite this